Structural organization of the DR subregion of the human major histocompatibility complex

Abstract

Two clusters of overlapping cosmid and λ phage clones comprising 205 kilobases (kb) have been isolated from the DR subregion of the human major histocompatibility complex from a DR4 haplotype. A single DRα and three DRβ genes were identified. In one cluster (135 kb), the DRα gene is 90 kb distant from the DRβ gene encoding a molecule that carries the MT3 serological specificity. In the second cluster (70 kb), the DRβ gene determining the DR4 specificity is located 22 kb apart from a DRβ pseudogene (DRβψ). A 3- to 4-kb sequence located at the 5' end of the DRβ(MT3) gene is common to all three DRβ-chain genes. In addition, three more copies of this sequence are spaced between the DRα and the DRβ (MT3) genes in the first cluster and one of these, at least, is associated with a DRβ1 exon, suggesting that additional genes could be encoded in this region and that multiple duplication events have led to its evolution.